| Autor: |
Chermside-Scabbo CJ; Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.; Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, USA., Shuster JT; Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Erdmann-Gilmore P; Department of Medicine, Proteomics Core, Washington University School of Medicine, St. Louis, MO 63110, USA., Tycksen E; Department of Genetics, McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA., Zhang Q; Department of Medicine, Proteomics Core, Washington University School of Medicine, St. Louis, MO 63110, USA., Townsend RR; Department of Medicine, Proteomics Core, Washington University School of Medicine, St. Louis, MO 63110, USA., Silva MJ; Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.; Department of Biomedical Engineering, Washington University, St. Louis, MO 63105, USA. |
| Abstrakt: |
With aging, bone mass declines and the anabolic effects of skeletal loading diminish. While much research has focused on gene transcription, how bone ages and loses its mechanoresponsiveness at the protein level remains unclear. We developed a novel proteomics approach and performed a paired mass spectrometry and RNA-seq analysis on tibias from young-adult (5-month) and old (22-month) mice. We report the first correlation estimate between the bone proteome and transcriptome (Spearman ρ = 0.40), which is in line with other tissues but indicates that a relatively low amount of variation in protein levels is explained by the variation in transcript levels. Of 71 shared targets that differed with age, eight were associated with bone mineral density in previous GWAS, including understudied targets Asrgl1 and Timp2. We used complementary RNA in situ hybridization to confirm that Asrgl1 and Timp2 had reduced expression in osteoblasts/osteocytes in old bones. We also found evidence for reduced TGF-beta signaling with aging, in particular Tgfb2. Next, we defined proteomic changes following mechanical loading. At the protein level, bone differed more with age than with loading, and aged bone had fewer loading-induced changes. Overall, our findings underscore the need for complementary protein-level assays in skeletal biology research. |
